Scientists Just Found a Previously Unknown Nerve Pathway For Pain

MIKE MCRAE

12 DEC 2018

To ease the sting of a paper cut, most of us will instinctively pop the afflicted finger in the mouth and suck for a moment or two. We rub barked shins, cool blistered skin, and shake a crushed hand. And it might represent a completely different kind of pain.

A pathway of nerves recently identified in mice appears to be responsible for the sustained ache we experience after the initial shock of pain has faded, and it could help explain why some painkillers aren't living up to expectation.

Harvard Medical School researchers led a study on different ways painful stimuli travel from the site of trauma to the brain, seeking to better understand the various circuits responsible for creating acute and chronic discomfort.

Whether it's a stubbed toe, a prickle in your foot, or grabbing a hot utensil, the basic response is the same – our body reflexes tell us to move away from the source of danger.

The sharp burst of agony known as nociception might last a brief moment, but it's enough to force us to pull away and prevent the risk of further damage.

But after that initial burst, depending on the severity of the trauma, we can experience seconds, minutes, or even days of persistent discomfort. Sometimes we apply pressure, or cool the wound, to alleviate the pain.

Dana-Farber Cancer Institute neurobiologist Qiufu Ma has devoted years to researching the nervous routes of pain and itching. His studies have led him and his team to suspect those two different types of pain follow different paths.

It's no secret that our perception of traumatic stimuli is the result of some pretty complex neurology involving sensory nerves called nociceptors and various pathways that carry signals to the spinal cord and areas of the brain.

But the details remain somewhat foggy. For example, is a 'pain matrix' of locations in the brain primarily responsible for our hurt, or is the story more complicated than it first appears?

Similarly, are different flavours of suffering mediated by different systems of nerves, or is it all in the processing?

To add to the evidence of distinct highways of nociception, Ma and his team looked to a category of spinal nerves that had been previously associated with noxious stimuli.

A gene expressed in these cells called Tac1 stood out as potentially having a key role in the neurons' function. The natural way to see what a gene does is to switch it off and watch what happens. Doing this in humans is fairly problematic, but mice pose fewer practical or ethical dilemmas.

Strangely, mice engineered to have their Tac1 gene silenced still showed a response to pain. Having their feet pricked, pinched, or dosed with mustard oil still resulted in clear signs of aversion.

But unlike mice with their Tac1 intact, these tiny test subjects didn't bother nursing their wounds by licking the afflicted skin, suggesting these spinal nerves might play a role in informing the brain of recent physical damage.

Tracing them to the periphery, the team found there was still a segregation of nerves, suggesting a completely distinct pathway all the way from the source.

Those nerves were already familiar thanks to their capsaicin receptors, called TrpV1. Not only do they respond to temperature, and spicy chemicals that trigger a sensation of heat, they become more sensitive in the presence of mediating chemicals released by inflammation.

Having distinct pathways for the initial burst of pain and for the persistent discomfort could explain why some potential pain-busting pharmaceuticals look good on animal trials, but don't do much to alleviate ongoing aching, stinging, and burning sensations.

Many drugs are based on the initial responses of animals to pain – a clear withdrawal of a foot, for example. But fewer pay attention to what the team refers to as coping mechanisms that might demonstrate lingering discomfort.

It's an interesting find, but the convenience of using mice also throws up the problem of accurately interpreting the results. Licking behaviours make a good proxy for 'coping' with pain, but it's not like we can ask them.